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A special issue of Cancers (ISSN 2072-6694).

Deadline for manuscript submissions: closed (31 March 2020) | Viewed by 16778

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Prof. Dr. Hajime Isomoto

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Division of Medicine and Clinical Science, Faculty of Medicine, Tottori University, Yonago, Tottori 683-8504, Japan
Interests: endoscopic diagnoses and therapies for gastrointestinal neoplasia; advanced endoscopy; clinical and molecular imaging; esophageal squamous cell carcinoma; esophageal achalasia; chronic inflammation and carcinogenesis in the alimentary tract; photodynamic diagnosis and photodynamic therapy
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Special Issue Information

Dear colleagues,

Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive squamous cell carcinomas, requiring a multidisciplinary approach. Chemoradiotherapy has supplemented surgery as standard treatment of locally advanced ESCC. Local failure can be alternatively salvaged via photodynamic therapy. Cancer vaccines and immune checkpoint inhibitors are employed at present. Endoscopic resection is the preferred modality for early disease confined to the mucosa not involving the muscularis mucosa. Image-enhanced endoscopy with/without (ultra) magnification has merits for accurate predilection of ESCC invasion depth, substituting conventional iodine-staining or exceeding endoscopic ultrasound sonography. Artificial intelligence allows evolutions in the ESCC diagnostic field. State-of-art molecular–biologic technologies such as comprehensive genome-wide sequencing offer insights into the extent of genetic mutations in the epithelial tissue even from healthy esophagus, and how this relates to processes that drive ESCC development. The Special Issue will open doors to more recent advances gained from basic and clinical research.

Prof. Hajime Isomoto
Guest Editor

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Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

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Keywords

esophageal squamous cell carcinoma
carcinogenesis
advanced endoscopic diagnosis
endoscopic resection
photodynamic therapy
immunotherapies
artificial intelligence

Published Papers (6 papers)

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Editorial

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3 pages, 189 KiB

Open AccessEditorial

Current Topics in Esophageal Squamous Cell Carcinoma

by Hiroki Kurumi and Hajime Isomoto

Cancers 2020, 12(10), 2898; https://doi.org/10.3390/cancers12102898 - 09 Oct 2020

Cited by 9 | Viewed by 1583

Abstract

Esophageal squamous cell carcinoma (ESCC) is one of the most deadly cancers due to its extremely aggressive nature and poor survival rate. Central to East Asia is one of regions with the highest incidence of ESCC. In these five papers, the international leaders of ESCC in Asia have taken various approaches to ESCC. Lin et al. compared intensity-modulated radiation therapy with three-dimensional stereoscopic radiation therapy with respect to treatment of ESCC. Song et al. demonstrated that (S)-10-Hydroxycamptothecin is useful in the ESCC cell lines as well as in vivo using a patients-derived xenograft tumor model in mice. Chen et al. showed Stromal cell-derived factor-1α expression is an independent prognostic predictor of ESCC. Lin et al. showed that the SUV_LN/SUV_Tumor ratio of PET-CT was associated with ESCC prognosis. Yoon et al. investigated the association between sarcopenia and prognosis in the ESCC patients. All reports are an essential approach to overcoming ESCC. Full article

(This article belongs to the Special Issue Esophageal Squamous Cell Carcinoma)

Research

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11 pages, 2372 KiB

Open AccessArticle

Prognostic Value of SDF-1α Expression in Patients with Esophageal Squamous Cell Carcinoma Receiving Esophagectomy

by Yen-Hao Chen, Shau-Hsuan Li, Hung-I Lu and Chien-Ming Lo

Cancers 2020, 12(5), 1067; https://doi.org/10.3390/cancers12051067 - 25 Apr 2020

Cited by 5 | Viewed by 1925

Abstract

Stromal cell-derived factor-1α (SDF-1α) is a chemokine that has been reported to be involved in tumor progression in several malignancies. This study aimed to evaluate the crucial role of SDF-1α in patients with esophageal squamous cell carcinoma (ESCC) who underwent esophagectomy. A total of 169 patients with ESCC were identified, including overexpression of SDF-1α in 60 patients and low expression of SDF-1α in 109 patients by immunohistochemical analysis. Two ESCC cell lines, TE1 and KYSE30, were selected to evaluate the tumor cell proliferative effect of SDF-1α. Univariate and multivariate analyses showed that high tumor (T) status, positive lymph node metastasis, tumors located in the upper esophagus, and SDF-1α overexpression were significantly related to worse disease-free survival and overall survival. In addition, the two cell lines were treated with SDF-1α, AMD3100 (an SDF-1α-ligand receptor antagonist), and chemotherapeutic agents (cisplatin). Our in vitro study results showed that SDF-1α promoted the proliferation of tumor cells, and blocking the SDF-1α pathway displayed a growth inhibition effect in a dose-dependent manner. SDF-1α plays an important role in the progression of ESCC and is an independent prognostic factor for ESCC patients who underwent esophagectomy. Full article

(This article belongs to the Special Issue Esophageal Squamous Cell Carcinoma)

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14 pages, 555 KiB

Open AccessArticle

Prognostic Impact of Sarcopenia and Skeletal Muscle Loss During Neoadjuvant Chemoradiotherapy in Esophageal Cancer

by Han Gyul Yoon, Dongryul Oh, Yong Chan Ahn, Jae Myoung Noh, Hongryull Pyo, Won Kyung Cho, Yun Mi Song, Minsu Park, Na Young Hwang, Jong-Mu Sun, Hong Kwan Kim, Jae Ill Zo and Young Mog Shim

Cancers 2020, 12(4), 925; https://doi.org/10.3390/cancers12040925 - 10 Apr 2020

Cited by 35 | Viewed by 4032

Abstract

Backgrounds: The relationship between sarcopenia, characterized by loss of muscle mass and strength, and survival outcomes of esophageal cancer is controversial. This study aimed to assess the effect of sarcopenia and skeletal muscle loss on overall survival (OS) and recurrence-free survival (RFS) of esophageal cancer patients. Methods: We retrospectively collected the medical records of 248 male patients diagnosed with squamous cell esophageal cancer and who underwent neoadjuvant chemoradiotherapy (NACRT) followed by surgery. We measured the cross-sectional area of the skeletal muscle at the L3 vertebra level using computed tomography images and calculated the skeletal muscle index (SMI). Sarcopenia was defined as SMI <52.4 cm²/m², and excessive muscle loss was defined as SMI change <−10.0%/50 days during NACRT. Moreover, laboratory test results, such as albumin, prognostic nutritional index (PNI), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) before and after NACRT, were collected. Results: In the univariable Cox analysis, pre- (p = 0.689) and post-radiotherapy (RT) sarcopenia (p = 0.669) were not associated with OS. However, excessive muscle loss had a significant association with OS in both the univariable and multivariable analyses (all p = 0.001). Excessive muscle loss was also related to RFS in both the univariable (p = 0.011) and multivariable (p = 0.022) Cox analysis. Patients with excessive muscle loss had significantly lower levels of post-RT albumin (p < 0.001) and PNI (p < 0.001), higher levels of post-RT NLR (p = 0.031) and PLR (p = 0.071), larger decrease in albumin (p < 0.001) and PNI (p < 0.001) after NACRT, and larger increase in NLR (p = 0.051) and PLR (p = 0.088) after NACRT than in those with non-excessive muscle loss. Conclusion: Excessive muscle loss rather than pre- and post-RT sarcopenia was a significant prognostic factor for OS and RFS, and it was also related to nutritional and inflammatory markers. Full article

(This article belongs to the Special Issue Esophageal Squamous Cell Carcinoma)

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12 pages, 1223 KiB

Open AccessArticle

Prognostic Value of Lymph Node-To-Primary Tumor Standardized Uptake Value Ratio in Esophageal Squamous Cell Carcinoma Treated with Definitive Chemoradiotherapy

by Chia-Hsin Lin, Tsung-Min Hung, Yu-Chuan Chang, Chia-Hsun Hsieh, Ming-Chieh Shih, Shih-Ming Huang, Chan-Keng Yang, Ching-Fu Chang, Sheng-Chieh Chan and Wing-Keen Yap

Cancers 2020, 12(3), 607; https://doi.org/10.3390/cancers12030607 - 06 Mar 2020

Cited by 10 | Viewed by 2777

Abstract

We aimed to investigate the prognostic value of the relative maximum standardized uptake value (SUV) of metastatic lymph node (LN) compared with that of primary tumor (SUV_LN/SUV_Tumor) based on a pretreatment [¹⁸F]-FDG PET/CT scan in patients with clinically node-positive esophageal squamous cell carcinoma (cN+ ESCC) treated with definitive chemoradiotherapy (dCRT). We retrospectively evaluated cN+ ESCC patients who underwent a PET/CT scan before dCRT. Time-dependent receiver operating characteristics analysis was performed to identify the optimal cutoff value for SUV_LN/SUV_Tumor. Prognostic influences of SUV_LN/SUV_Tumor on distant metastasis-free survival (DMFS) and overall survival (OS) were evaluated using the Kaplan–Meier method and log-rank test for univariate analysis and Cox’s proportional hazards regression model for multivariate analysis. We identified 112 patients with newly diagnosed cN+ ESCC. After a median follow-up of 32.0 months, 50 (44.6%) patients had distant failure and 84 (75.0%) patients died. Patients with high SUV_LN/SUV_Tumor (≥ 0.39) experienced worse outcomes than low SUV_LN/SUV_Tumor (< 0.39) (two-year DMFS: 26% vs. 70%, p < 0.001; two-year OS: 21% vs. 48%, p = 0.001). Multivariate analysis showed that SUV_LN/SUV_Tumor was an independent prognostic factor for both DMFS (adjusted HR 2.24, 95% CI 1.34–3.75, p = 0.002) and OS (adjusted HR 1.61, 95% CI 1.03–2.53, p = 0.037). Pretreatment of SUV_LN/SUV_Tumor is a simple and useful marker for prognosticating DMFS and OS in cN+ ESCC patients treated with dCRT, which may help in tailoring treatment and designing future clinical trials. Full article

(This article belongs to the Special Issue Esophageal Squamous Cell Carcinoma)

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15 pages, 4747 KiB

Open AccessArticle

(S)-10-Hydroxycamptothecin Inhibits Esophageal Squamous Cell Carcinoma Growth In Vitro and In Vivo Via Decreasing Topoisomerase I Enzyme Activity

by Mengqiu Song, Shuying Yin, Ran Zhao, Kangdong Liu, Joydeb Kumar Kundu, Jung-Hyun Shim, Mee-Hyun Lee and Zigang Dong

Cancers 2019, 11(12), 1964; https://doi.org/10.3390/cancers11121964 - 06 Dec 2019

Cited by 15 | Viewed by 2737

Abstract

Topoisomerase (TOP) I plays a major role in the process of supercoiled DNA relaxation, thereby facilitating DNA replication and cell cycle progression. The expression and enzymatic activity of TOP I is positively correlated with tumor progression. Although the anticancer activity of (S)-10-Hydroxycamptothecin (HCPT), a TOP I specific inhibitor, has been reported in various cancers, the effect of HCPT on esophageal cancer is yet to be examined. In this study, we investigate the potential of HCPT to inhibit the growth of ESCC cells in vitro and verify its anti-tumor activity in vivo by using a patient-derived xenograft (PDX) tumor model in mice. Our study revealed the overexpression of TOP I in ESCC cells and treatment with HCPT inhibited TOP I enzymatic activity at 24 h and decreased expression at 48 h and 72 h. HCPT also induced DNA damage by increasing the expression of H2A.X^S139. HCPT significantly decreased the proliferation and anchorage-independent growth of ESCC cells (KYSE410, KYSE510, KYSE30, and KYSE450). Mechanistically, HCPT inhibited the G2/M phase cell cycle transition, decreased the expression of cyclin B1, and elevated p21 expression. In addition, HCPT stimulated ESCC cells apoptosis, which was associated with elevated expression of cleaved PARP, cleaved caspase-3, cleaved caspase-7, Bax, Bim, and inhibition of Bcl-2 expression. HCPT dramatically suppressed PDX tumor growth and decreased the expression of Ki-67 and TOP I and increased the level of cleaved caspase-3 and H2A.X^S139 expression. Taken together, our data suggested that HCPT inhibited ESCC growth, arrested cell cycle progression, and induced apoptosis both in vitro and in vivo via decreasing the expression and activity of TOP I enzyme. Full article

(This article belongs to the Special Issue Esophageal Squamous Cell Carcinoma)

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Graphical abstract

15 pages, 534 KiB

Open AccessArticle

Three-Dimensional Conformal Radiotherapy-Based or Intensity-Modulated Radiotherapy-Based Concurrent Chemoradiotherapy in Patients with Thoracic Esophageal Squamous Cell Carcinoma

by Wei-Cheng Lin, Chia-Lun Chang, Han-Lin Hsu, Kevin Sheng-Po Yuan, Alexander T. H. Wu and Szu-Yuan Wu

Cancers 2019, 11(10), 1529; https://doi.org/10.3390/cancers11101529 - 10 Oct 2019

Cited by 9 | Viewed by 3046

Abstract

Background: To date, intensity-modulated radiation therapy (IMRT) with concurrent chemoradiotherapy (CCRT) and CCRT with standard fractionation three-dimensional conformal radiation therapy (3D-CRT) have not been compared. In this study, the outcomes of IMRT-based concurrent CCRT and those of 3D-CRT-based CCRT were compared in patients with thoracic esophageal squamous cell carcinoma (TESCC). Methods: We enrolled 2062 patients with TESCC who had received CCRT and categorized them into two groups on the basis of their treatment modality: Group 1 (3D-CRT-based CCRT) and Group 2 (IMRT-based CCRT). Results: Multivariate Cox regression analysis indicated that the American Joint Committee on Cancer advanced stages (≥IIIA) and 3D-CRT were significant independent predictors of poor outcomes in patients with TESCC who received definitive CCRT. Moreover, receiving IMRT-based CCRT (adjusted hazard ratio [aHR]: 0.88, 95% confidence interval [CI]: 0.78–0.98) was a significant independent prognostic factor for overall survival (p = 0.0223). In Group 2, aHRs (95% CIs) for overall mortality at early (IA–IIB) and advanced clinical stages were 0.91 (0.67–1.25, p = 0.5746) and 0.88 (0.77–0.99, p = 0.0368), respectively. Conclusion: IMRT-based CCRT resulted in higher survival rates in patients with advanced clinical stages of TESCC (i.e., IIIA–IIIC), namely, clinical T3, clinical T4, or lymph node involvement. Full article

(This article belongs to the Special Issue Esophageal Squamous Cell Carcinoma)

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